Maintenance therapy with Revlimid® (lenalidomide) has been shown to significantly improve progression-free survival and time to progression in multiple myeloma, according to the results of three studies published in the New England Journal of Medicine.
Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.
Revlimid is an oral medication that can stop or slow the growth of cancerous myeloma cells within the bone marrow. It has been approved in combination with dexamethasone for multiple myeloma patients who have received at least one prior therapy. Revlimid has been associated with an increased risk of new cancers and the FDA recently made a safety announcement regarding the drug.
Despite the increased risk of new cancers, Revlimid continues to be studied for its use as maintenance therapy in multiple myeloma. Three double-blind, phase 3, multi-center, randomized trials evaluated Revlimid maintenance therapy. Two studies randomly assigned patients to Revlimid or placebo after stem-cell transplantation. The third study included patients who were ineligible for stem-cell transplantation; these patients were randomly assigned to Revlimid or placebo after oral induction therapy. In all three studies, study-drug assignments were unblended early after Revlimid maintenance showed significant benefit.
In the first study, researchers assigned 614 patients under age 65 to Revlimid or placebo after transplantation. They found that maintenance therapy with Revlimid improved progression-free survival, with a progression-free survival of 41 months in the Revlimid group compared to 23 months in the placebo group. After a median follow-up of 45 months, more than 70 percent of patients in both groups were alive at 4 years. There was an increased rate of new cancers in the Revlimid group, with 32 new cancers in the Revlimid group and 12 in the placebo group. However, the researchers concluded that the benefit of Revlimid outweighed the risk of new cancers.
In the second study, 460 patients age 71 or younger were randomly assigned to Revlimid or placebo after transplantation. Patients in the Revlimid group had a significantly longer time to disease progression compared to those in the placebo group—the median time to progression was 46 months in the Revlimid group and 27 months in the placebo group. Patients in the Revlimid group experienced more grade 3 and 4 adverse events and 18 (8%) patients in the Revlimid group had second primary cancers, compared with 6 (3%) in the placebo group. A total of 35 patients who received Revlimid (15%) and 53 patients who received placebo (23%) died.
The third study involved patients who were ineligible for transplantation. In this study, patients were randomly assigned to one of three groups:152 patients received oral melphalan-prednisone-Revlimid induction followed by Revlimid (MPR-R); 153 patients patients received oral melphalan-prednisone-Revlimid followed by placebo (MPR); and 154 patients received melphalan-prednisone followed by placebo (MP). The median progression-free survival was significantly longer with Revlimid maintenance therapy—the MPR-R group had a median progression-free survival of 31 months, compared to 14 months for the MPR group and 13 months for the MP group. The rate of new cancers was 7% with MPR-R, 7% with MPR, and 3% with MP.
In an accompanying editorial, Ashraf Badros notes that while Revlimid appears to offer benefit as maintenance therapy for multiple myeloma, it does come with risks, namely the increased risk of second primary cancers. Furthermore, he questions whether progression-free survival is the optimal endpoint for maintenance therapy and whether it is the most cost-effective treatment.
 FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies [FDA Safety Announcement]. U.S. Food and Drug Administration website. Available at:
 Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma. New England Journal of Medicine. 2012; 366:1782-1791.
 McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma. New England Journal of Medicine. 2012; 366:1770-1781.
 Palumbo A, Hajek R, Delforge M, et al. Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma. New England Journal of Medicine. 2012; 366:1759-1769.
 Badros AZ. Lenalidomide in Myeloma — A High-Maintenance Friend
New England Journal of Medicine. 2012; 366:1836-1838.
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